A PhaseⅠ/Ⅱ Study of Simmitinib or Irinotecan Liposomes Combined With DP303c in Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma

Official title

A Multicenter, Open-label Phase I/II Clinical Study to Evaluate the Safety and Efficacy of Simmitinib or Irinotecan Liposomes Combined With DP303c Injection in the Treatment of HER2 Expressing Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma

Overview

This study is divided into two parts: Cohort 1 and Cohort 2. Cohort 1 includes the dose escalation phase of DP303c combined with simmitinib, as well as the randomized controlled trial (RCT) phase of DP303c combined with simmitinib; Cohort 2 includes dose escalation/dose extension of DP303c combined with irinotecan liposomes, as well as RCT stage of DP303c combined with irinotecan liposomes.

Interventions

• Drug DP303c
  DP303c is an antibody conjugate drug (ADC), composed of one anti-HER2 monoclonal antibody coupled to one MMAE via an enzyme specific linker
• Drug Simmitinib tablets
  A novel small molecule inhibitor targeting fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR2, KDR), and colony-stimulating factor 1 receptor (CSF-1R)
• Drug Irinotecan liposomes
  A chemotherapy
• Drug Paclitaxel or docetaxel or irinotecan
  Paclitaxel or docetaxel or irinotecan is used as a control.

Primary outcome measures

• Dose-limiting toxicity(DLT) occurrence and incidence [Time frame: Up to approximately 36 months after the first participant is enrolled]
• Adverse events (AE) occurrence and incidence [Time frame: Up to approximately 36 months after the first participant is enrolled]
• Objective response rate (ORR) per RECIST 1.1 [Time frame: Up to approximately 36 months after the first participant is enrolled]
• Serious adverse events (SAE) occurrence and incidence [Time frame: Up to approximately 36 months after the first participant is enrolled]

Secondary outcome measures (9)

• Disease control rate (DCR) per RECIST 1.1 [Time frame: Up to approximately 36 months after the first participant is enrolled]
• Duration of response (DoR) per RECIST 1.1 [Time frame: Up to approximately 36 months after the first participant is enrolled]
• Progression free survival (PFS) per RECIST 1.1 [Time frame: Up to approximately 36 months after the first participant is enrolled]
• Overall survival(OS) [Time frame: Up to approximately 36 months after the first participant is enrolled]
• Blood drug concentration of DP303c [Time frame: Up to approximately 36 months after the first participant is enrolled]
• Blood concentration of total anti-DP303c antibody [Time frame: Up to approximately 36 months after the first participant is enrolled]
• Positive incidence of anti-DP303c antibody (ADA) [Time frame: Up to approximately 36 months after the first participant is enrolled]
• HER2 expression level [Time frame: Up to approximately 36 months after the first participant is enrolled]
• Blood concentration of simmitinib [Time frame: Up to approximately 36 months after the first participant is enrolled]

Eligibility criteria

Inclusion criteria

• 1\. Aged 18-75 (including) years old; 2. Gastric adenocarcinoma or gastroesophageal junction adenocarcinoma diagnosed by histology or cytology; 3. Disease progression after receiving one or two lines of systemic treatment in the past (first-line treatment must be platinum/fluorouracil combination chemotherapy with or without immune checkpoint inhibitors); 4. There should be at least one measurable lesion according to the response evaluation criteria in solid tumors (RECIST v1.1),; 5. HER2 expression status: 2+ to 3+(applicable to Cohort 1) or 1+(applicable to Cohort 2); 6. Adequate organ or bone marrow function

Exclusion criteria

• \*Eligibility Criteria:

Inclusion criteria

• Aged 18-75 (including) years old;
• Gastric adenocarcinoma or gastroesophageal junction adenocarcinoma diagnosed by histology or cytology;
• Disease progression after receiving one or two lines of systemic treatment in the past (first-line treatment must be platinum/fluorouracil combination chemotherapy with or without immune checkpoint inhibitors);
• There should be at least one measurable lesion according to the response evaluation criteria in solid tumors (RECIST v1.1),;
• HER2 expression status: 2+ to 3+(applicable to Cohort 1) or 1+(applicable to Cohort 2);
• Adequate organ or bone marrow function

Exclusion criteria

• Patients who have experienced toxicity during previous treatment with trastuzumab or trastuzumab biosimilars, resulting in permanent discontinuation of trastuzumab or trastuzumab biosimilars;
• Patients with a history of allergies to any component of DP303c and deemed severe by the researchers
• There is uncontrolled serosal fluid accumulation that requires frequent drainage or medical intervention;
• Active leptomeningeal disease or uncontrolled CNS metastasis;
• Has a history of serious cardiovascular and cerebrovascular diseases;
• There was a peripheral neuropathy of grade ≥ 2 (refer to NCI CTCAE 5.0) prior to enrollment;
• History of gastrointestinal perforation and/or fistula within 6 months of first use of medication;
• Inability to swallow medication orally or presence of clinically significant gastrointestinal diseases;
• Urine protein ≥++ and 24-hour urine protein quantification>1.0 g during screening period;
• There are eye diseases that require intervention, such as corneal diseases, retinal diseases, or active eye infections;
• Used CYP3A4 strong inhibitors or CYP3A4 strong inducers 14 days before the first medication ;
• Used UGT1A1 strong inhibitor before first medication and wash-off period is less than 5 half-lives.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06577376 · SYSA1501-010

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗